Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D plays a pivotal role in the pathogenesis and treatment of renal bone disease. Vitamin D levels decline in the early phase of renal failure, however, through a compensatory mechanism parathyroid hormone (PTH) stimulates the production of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) to return it to normal circulating concentrations. Nevertheless, resistance to calcitriol is observed and may be related to the decreased presence of the heterodimeric, DNA-binding partner for the vitamin D receptor protein. In end-stage kidney disease (ESKD) the circulating levels of calcitriol are invariably low. The indications of vitamin D therapy are the replacement of the missing hormone vs suppression of hyperparathyroidism (HPT) requiring daily low-dose oral vs intermittent 'pulse' or oral administration. However, this therapy must be accompanied by careful patient monitoring to avoid hypercalcaemia and low bone turnover. Low bone turnover is not merely a histologic entity, but a clinical condition associated with a high risk of extraosseous calcifications, in particular in the cardiovascular system, leading to increased morbidity. Thus, determination of bone turnover in patients with ESKD is essential. Bone biopsy is the gold standard to assess bone turnover, however, it is not always available and nephrologists rely on PTH levels. The intact PTH assay measures PTH(1-84) and large C-PTH fragments, which may antagonize the PTH(1-84) effects on bone. An assay that measures exclusively PTH(1-84) has recently become available and a calculated PTH(1-84)/C-PTH fragment ratio has been shown to be the best predictor of bone turnover in patients with ESKD not treated with vitamin D or with other medications known to affect bone metabolism. 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is a vitamin D analogue that could control serum PTH concentrations without deleterious effects on bone.
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PMID:Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease. 1238 63

A trial on the long-term administration of 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitoriol, OCT) was conducted among 124 patients with chronic renal failure on maintenance haemodialysis (HD) complicated with secondary hyperparathyroidism (2HPT). In the trial, OCT was administered three times weekly for 26 weeks subsequent to a 26-week pre-trial. As a result, intact-parathyroid hormone (PTH) levels fell significantly after the start of administration and, at the end of the trial, PTH was decreased by over 30% in 51.6% (64/124) of the patients, and the levels of bone metabolism markers such as alkaline phosphatase (ALP), bone ALP, and tartrate-resistant acid phosphatase (TRACP) were significantly decreased compared with those at the start of administration, suggesting a correction of high-turnover bone disease. Serum calcium (Ca) levels rose significantly following OCT administration, but were successfully maintained within a physiological level. Hypercalcaemia, which was diagnosed in 33.1% of patients, was found to resolve or ameliorate immediately after the withdrawal or dose reduction of OCT. OCT can be administered for as long as 1 year without any major problems other than hypercalcaemia. The final doses ranged from 2.5 to 20.0 microg/HD, and the optimal dose varied among patients depending on the intact-PTH and adjusted serum Ca levels. These results suggest that OCT is a highly effective drug for the suppression of PTH levels in 2HPT, and is an overall safe drug if the dosage is adjusted for serum Ca and intact-PTH levels. This study confirmed that the long-term (1-year) administration of OCT is very useful for the treatment of 2HPT.
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PMID:Long-term effect of 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in haemodialysis patients. One-year administration study. 1238 66

A trial on the long-term administration of 22-oxacalcitriol (maxacalcitol, OCT) was conducted among 124 patients with chronic renal failure on maintenance hemodialysis (HD) complicated with secondary hyperparathyroidism (2 degrees HPT ). In the trial, OCT was administered 3 times weekly for 26 weeks subsequent to a 26-week pre-trial. As a result, intact-parathyroid hormone (PTH) levels fell significantly after the start of administration and were well controlled for one year. The levels of markers of bone metabolism such as bone alkaline phosphatase were decreased significantly compared with those at the start of administration, suggesting a correction of high-turnover bone disease. Serum calcium (Ca) levels rose significantly following OCT administration, but were successfully maintained within a physiological range. Hypercalcemia, in 33.1% of patients, was found to resolve or ameliorate immediately after the withdrawal or dose reduction of OCT. The final doses ranged from 2.5 mg to 20 mg/HD, and the optimal dose varied among patients depending on the intact-PTH and serum Ca levels. These results clearly suggest that OCT is a highly effective drug for the treatment of 2 degrees HPT, and is an overall safe drug if the dosage is adjusted for serum Ca and intact-PTH levels.
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PMID:[Long-term clinical effect of maxacalcitol on hemodialysis patients with secondary hyperparathyroidism]. 1577 67